chr7-107713909-GTAT-G

Variant names:

• chr7-107713909-GTAT-G
• rs34694220
• NM_000441.2:c.2319+1307_2319+1309delATT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000441.2(SLC26A4):​c.2319+1307_2319+1309delATT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene SLC26A4 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.51 (19828 hom., cov: 0)
• Consequence: SLC26A4 NM_000441.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.421
• Publications: 0 publications found

Genes affected

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

SLC26A4 Gene-Disease associations (from GenCC):

• autosomal recessive nonsyndromic hearing loss 4

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Pendred syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• athyreosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• thyroid hypoplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Specifications for SLC26A4 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000441.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	NM_000441.2	MANE Select	c.2319+1307_2319+1309delATT		intron	N/A	NP_000432.1	O43511-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A4	ENST00000644269.2	MANE Select	c.2319+1288_2319+1290delTAT		intron	N/A	ENSP00000494017.1	O43511-1
	SLC26A4	ENST00000888701.1		c.2319+1288_2319+1290delTAT		intron	N/A	ENSP00000558760.1
	SLC26A4	ENST00000888700.1		c.2241+1288_2241+1290delTAT		intron	N/A	ENSP00000558759.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 75761 AN: 148788 Hom.: 19821 Cov.: 0

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.475

Gnomad EAS AF: 0.638

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.498

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.509 AC: 75797 AN: 148868 Hom.: 19828 Cov.: 0 AF XY: 0.508 AC XY: 36861 AN XY: 72538

African (AFR) AF: 0.642 AC: 25794 AN: 40174

American (AMR) AF: 0.466 AC: 6944 AN: 14904

Ashkenazi Jewish (ASJ) AF: 0.475 AC: 1638 AN: 3452

East Asian (EAS) AF: 0.637 AC: 3204 AN: 5030

South Asian (SAS) AF: 0.391 AC: 1836 AN: 4700

European-Finnish (FIN) AF: 0.466 AC: 4660 AN: 9994

Middle Eastern (MID) AF: 0.375 AC: 108 AN: 288

European-Non Finnish (NFE) AF: 0.448 AC: 30151 AN: 67358

Other (OTH) AF: 0.495 AC: 1025 AN: 2070

Alfa AF: 0.231 Hom.: 408

Bravo AF: 0.520

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs34694220; hg19: chr7-107354354;